Vitamin B1 Thiamine

By Richard S. Bak, Ph.D.

Introduction

Vitamin B1 (Thiamine) is a
water-soluble vitamin of the B group. In
animal tissues, it is present mainly in
phosphorylated form, with thiamine
pyrophosphate being the most abundant.
The pyrophosphate form is
a coenzyme of five different
enzymes involved in
carbohydrate and lipid
metabolism. Vitamin B1 is
absorbed by the small
intestine by a specific,
easily saturable mechanism,
which can be impaired by
alcohol, and by synthetic or
natural thiamine
antagonists present in food.

Thiamine deficiency
can develop after only one
month of a thiamine free
diet. Mild thiamine deficiency occurs in
pregnant women (increased requirement), in
alcoholics, the elderly, persons who have
persistent vomiting or gastric suction, those
with chronic illnesses such as cancer,
patients taking diuretics, and those who go on a long fast. Severe thiamine deficiency is called beriberi
and is characterized by peripheral neuritis or cardiac failure.
In undeveloped countries, the main cause of severe thiamine
deficiency is inadequate intake due to a diet consisting
primarily of polished rice. In industrialized countries,
however, the most common cause of severe thiamine
deficiency is alcoholism.

Chemistry

The structure of thiamine (vitamin B1) (3-[4-amino-2-
methyl-pyrimidyl-5-methyl]-4-methyl-5-[β-hydroxy-ethyl]
thiazole) is that of a pyrimidine ring, bearing an amino
group, linked by a methylene bridge to a thiazole ring. The
thiazole ring has a primary alcohol side chain, which can be
phosphorylated in vivo to produce thiamine phosphate esters, the most common of which is
thiamine pyrophosphate (Figure 1).
Monophosphate and triphosphate esters
also occur.

Figure 1. Thiamine pyrophosphate

Dietary Sources

All plant and animal tissues contain
vitamin B1, and so the vitamin is present in
all natural unprocessed foods. Rich sources
of vitamin B1 include yeast, pork, legumes,
beef, whole grains, oatmeal,
and nuts. Milled cereals and
milled and polished rice
contain little thiamine, if
any (1). Thiamine deficiency is
therefore more common in
cultures that rely heavily on
a rice-based diet.

Certain foods such as
tea, coffee, raw fish, and
shellfish contain thiamineases, which can
destroy the vitamin. Thus, drinking large
amounts of tea or coffee can lower thiamine
body stores (2).

Biological Functions

The biologically active form of thiamine is thiamine
pyrophosphate (Vitamin B1, thiamine diphosphate). It
functions as a co-enzyme (a co-carboxylase) in the oxidative
decarboxylation of pyruvate to form acetate and acetyl
co-enzyme A, and in the oxidative decarboxylation of
alpha-keroglutarate to succinyl Co A. Blocking the first
metabolic reaction results in impaired nerve transmission.
Blocking the second reaction results in anaerobic metabolism
with subsequent increases in blood pyruvate and lactate.

Thiamine pyrophosphate also functions as the coenzyme
for the enzyme transketolase, an enzyme involved in the
pentose monophosphate pathway. This metabolic pathway
supplies pentose phosphate for nucleotide synthesis, as well
as reduced nicotinamide adenine dinucleotide phosphate
(NADPH), an important electron donor in reductive
biosynthesis.

Thiamine also has a non-coenzymatic role in nerve
function as is evidenced by signs of thiamine deprivation
which are mainly neurological. The biochemical nature of
this role is still unclear.

Mild Deficiency

Although severe thiamine deficiency is
rare today, large segments of the world’s
population continue to subsist on marginal
or sub-marginal intake of thiamine. People
exposed to subclinical thiamine deficiency
are predisposed to manifest severe
deficiency under appropriate circumstances.

Mild thiamine deficiency can be seen in
people who have high carbohydrate intakes
and low thiamine intakes e.g. in people
whose staple food is polished rice, especially
if their diet contains anti-thiamine factors
(tea, coffee, raw fish) and in population
groups who consume large quantities of
sweetened carbonated drinks and candies (3).

Mild deficiency may also be seen in patients with
congestive heart failure treated with diuretics (5, 6, 7). Recently it
has been suggested that patients with Alzheimer’s disease
may be thiamine deficient (8, 9, 10), but these studies are weak and
contradictory. Whether thiamine supplementation is of
benefit in Alzheimer’s Disease remains controversial.

Characteristic early symptoms of thiamine deficiency
appear after 2 to 3 weeks of a deficient diet and include
anorexia, irritability, fatigue, aching, burning sensation in
the hands and feet, indigestion, sleep disturbances, and
depression. After 6 to 8 weeks the only objective signs at rest
may be a slight fall in blood pressure and moderate weight
loss. After 2 to 3 months apathy and weakness become
extreme, calf muscle tenderness develops with loss of recent memory, confusion, ataxia, and sometimes
persistent vomiting (3).

Severe Deficiency

Severe thiamine deficiency is called
beriberi. Three main types are recognized:
“dry” or neuritic, “wet” or
edematous, and “infantile”
or acute.

Dry Beriberi

Dry beriberi is a
disease of the peripheral
nervous system involving
bilateral impairment of
sensory, motor, and reflex
functions. The neuropathy
begins in the feet and legs
and then extends up the
body. Early signs of dry
beriberi often include
sensations of pins and needles and
numbness in the feet. The legs, especially
the calves, feel heavy and weak so that
walking becomes uncomfortable. As the
disease progresses, there is a marked wasting of the leg
muscles and even slight pressure applied to the calves elicits
severe pain. The characteristic foot and wrist drop develop
and there may be complete flaccid paralysis of the lower, and
occasionally upper, extremities (1).

Wet Beriberi

In wet beriberi, thiamine deficiency affects the
cardiovascular system by causing arteriolar dilation
throughout the circulatory system and by weakening the
heart muscle. Physical signs of wet beriberi are indicative of
high output cardiac failure; they include tachycardia, rapid
circulation time, elevated peripheral venous pressure, and
widespread edema.

Infantile Beriberi

Infantile beriberi is rarely seen today but can occur in
breast-fed babies between the second and sixth month of life.
Vomiting is one of the most important early signs of infantile
beriberi. Other symptoms include constipation, agitation,
difficulty in breathing, and generalized edema (1). In severe
cases the child appears to be crying but no sound is heard or
only a thin whine. This characteristic feature, aphonia, is due
either to paralysis of the laryngeal nerve or to edema of the
vocal cords. A chronic, pseudomenningial form of beriberi which affects the central nervous system
and may cause convulsions occurs in older
infants aged 7 to 9 months.

Wernicke-Korsakoff Syndrome

The Wernicke-Korsakoff syndrome is a
thiamine deficiency disease associated with
chronic alcoholics who obtain more than
half their daily calories from ethanol. Binge
drinkers who eat normally between bouts are not prone to
the disease.
The Wernicke-Korsakoff syndrome has two
components, Wernickes’ disease and Korsakoffs’ psychosis.
Wernickes’ disease is characterized by a triad of clinical signs
– eye abnormalities, incoordination, and altered state of
consciousness. Korsakoffs’ psychosis is characterized by a
form of amnesia in which events of ordinary life are forgotten as quickly as they occur but the
events in the distant past are well
remembered. Another symptom,
confabulation (story-telling) is an attempt
by the patient to hide the amnesia.

The Determination of Thiamine
Status

Thiamine status can be assessed by
three types of tests: determination of
erythrocyte transketolase activity, the
urinary excretion of thiamine before
and after thiamine administration, and
serum, erythrocyte, or whole blood
thiamine levels.

Erthyrocyte transketolase activity is
usually measured by measuring the rate of
disappearance of D-ribose-5-phosphate, in
the presence of orcinol reagent, before and
after thiamine pyrophosphate (Vitamin B1)
supplementation. The percent increase in
activity is defined as the “TPP effect.” The
transketolase determination was onceconsidered the most reliable means of assessing thiamine
status, but is now considered inadequate due to
non-specificity, poor sensitivity, poor precision, and lack of
specimen stability.

The determination of the urinary excretion of thiamine
in a 4-hour specimen, before and after a 5 mg dose of
thiamine, has been used as a measure of thiamine status.
However, excretion of the water soluble vitamin can be
influenced by dietary intake, absorption, and other factors.
Because of these factors, and the inconvenience of sample
collection, this test is now considered obsolete.

Thiamine levels can be determined in serum or plasma,
but this method suffers from poor sensitivity and specificity
and serum thiamine levels reflect recent intake rather than an
assessment of total body stores of thiamine.

Since erythrocyte thiamine stores deplete at a similar
rate to other major organs (11) and since the erythrocyte
contains approximately 80% of the total thiamine content of
whole blood (12), mainly as the pyrophosphate, the analysis of
thiamine pyrophosphate in whole blood or erythrocytes is
the most appropriate measurement to assess thiamine status.

Whole blood thiamine levels are
determined, at Warde Medical Laboratory,
by oxidizing thiamine and its phosphate
esters to their corresponding thiochrome
derivatives. Thiochrome diphosphate
(Figure 2) is selectively measured by
separation on an HPLC
column followed by
fluorometric detection.
This method is sensitive
and specific and it measures
only the active form of
thiamine: thiamine
diphosphate (Vitamin B1).

Figure 2. Thiochromediphosphate

Summary

Thiamine (Vitamin B1)
is an essential vitamin
required for carbohydrate
and lipid metabolism. Thiamine is found in
many foods so deficiency develops
primarily due to poor nutrition. The
symptoms of mild deficiency are vague but
include loss of appetite, irritability, fatigue,
and sleep disturbances. Severe deficiency
occurs in undeveloped countries due to
diets consisting primarily of processed rice,
and in developed countries as a result of
alcoholism.
The most reliable laboratory test for
thiamine deficiency is the measurement of
thiamine pyrophosphate in whole blood.